l-proline and l-histidine co-catalyzed Baylis–Hillman reaction

Abstract

Baylis-Hillman reaction between an aldehyde and an activated alkene, such as alkyl vinyl ketones, acrylates, acrylonitrile, and vinylsulfones, giving the b-hydroxy-a-methylene carbonyl compounds, is a versatile and atom-economical carbon-carbon bond-forming reaction. This reaction usually is catalyzed by strong Lewis bases such as tertiary amines and suffers from slow reaction rate. In this paper the Baylis-Hillman reaction between arylaldehydes and methyl vinyl ketone was successfully realized by a catalytic amount of L-proline and L-histidine system to give the corresponding normal Baylis-Hillman adducts in moderate to high yields for the first time. The effects of solvent and reagent electro property on the yields of this reaction were also investigated. Proline and histidine are naturally widely present amino acids in food system; furthermore, aldehydes and activated alkenes can also be easily produced in food processing, so proline and histidine co-catalyzed Baylis-Hillman reaction may find application in explaining some phenomena in food processing.

Proline-Mediated Baylis–Hillman Reaction of Methyl Vinyl Ketone without a Co-catalyst under Solvent-Free Conditions

“…To our pleasant surprise, under solvent-free conditions, the reaction of 2 with p-nitrobenzaldehyde (1a) using 50 mol% proline at 60 °C proceeded smoothly and cleanly to afford 83% yield of the Baylis-Hillman adduct 3a in just 10 h (Table 1, entry 1). Unfortunately, as was the case with most other dual-catalysed reactions discussed above, [5][6][7] no induction of asymmetry in the product was observed under these conditions. 13 Similar yields of the same adduct could be achieved with a slightly lower stoichiometry of the ketone or upon running the reaction at a lower temperature for a longer duration (entries 2 and 3).…”

“…Similarly, Guo et al more recently reported an L-proline and L-histidine co-catalysed Baylis-Hillman reaction, in which the imidazole moiety, present in the side chain of the latter, presumably plays the role of the Lewis base. 6 In a deviation from the use of Lewis base as co-catalysts, Gruttadauria et al reported a proline-catalysed Baylis-Hillman reaction of methyl vinyl ketone with aryl aldehydes carried out in the presence of NaHCO 3 as an additive in DMF-H 2 O (9:1). 7 This was reported to be the first evidence of proline acting as a bifunctional catalyst in the Baylis-Hillman reaction between alkyl vinyl ketones and aryl aldehydes.…”

Structure Simulation and Host–Guest Interaction of Histidine-Intercalated Hydrotalcite–Montmorillonite Complex

“…It is believed that this field will make great progress in the near future. Histidine contained an imidazole ring that has been widely used as the catalyst for the Aldol reaction [24,25] and the Baylis-Hillman reaction [26,27]. In addition, it is also used in the fields of physiology, medicine [28][29][30][31], and chemical industry [32][33][34].…”